Within the brain the expression of GABA-A receptor subunits is cell specific. This phenomenon of GABA-A receptor gene expression may explain why pharmacological properties of GABA-A receptors vary in different brain regions. However, the `6 subunit is unique in the narrowness of its cellular distribution; this subunit is found only in cerebellar granule cells. Intriguingly, the pharmacology of the `6 subunit is highly selective; GABA-A receptor complexes containing this subunit only display high affinity to Ro15-4513 but not to other benzodiazepines or to ~- carbolines. Ro15-4513, as shown by previous studies, may be a selective antagonist for some alcohol actions, such as motor impairment. Thus, the pharmacological data and neuroanatomic localization both point to a role for the `6 subunit in alcohol-induced motor impairment, and the goal of this project is to understand this role. To accomplish this, we are blocking the translation of `6 mRNA using antisense oligonucleotides injected into the cerebral ventricle and then measuring alcohol's action to cause motor incoordination.